Hydrogen peroxide (H₂O₂) appears to be ubiquitous in natural water. Higher level of H₂O₂ can cause physiological stress, immunosuppression and even death in aquatic animals, but the physiological and molecular mechanisms of H₂O₂ toxicity are not well studied. Thus, the aim of the present study was to exposure potential toxic mechanisms of H₂O₂ via assessing the effects on redox state, apoptosis and endoplasmic reticulum (ER) stress in common carp. The fish were subjected to four concentrations of H₂O₂ (0, 0.25, 0.5 and 1 mM) for 14 days. And then, the tissues including blood, liver, muscle, gills, intestines, heart, kidney and spleen were collected to measure biochemical parameter and gene expression. The results showed that H₂O₂ exposure suppressed the majority antioxidative parameters in serum, liver, muscle and intestines, but enhanced T-SOD, CAT and T-AOC levels in gills. In all tested tissues, the MDA content was significantly promoted by H₂O₂ exposure. The oxidative stress-related genes including nrf2, gstα, sod, cat and/or gpx1 were upregulated in liver, gills, muscle, intestines, and/or kidney, but downregulated in heart after H₂O₂ exposure. Moreover, the ho-1 mRNA level was inhibited by H₂O₂ exposure in all tissues except intestines and spleen. After 14 days of exposure, H₂O₂ induced ER stress and initiated IRE1 and PERK pathways, which activated downstream genes, including chop, grp78 and/or xbp1s, to regulate UPR in liver, gills, muscle and/or heart. Meanwhile, H₂O₂ exposure activated MAPK pathway to regulate mitochondria-related genes including bcl-2, bax and cytc, which further triggered cas-8, cas-9 and cas-3, and accelerated apoptosis in liver, gills, muscle and heart. Importantly, in different tissues, the genes associated with oxidative stress, ER stress and apoptosis showed a different influence, and more significant influence was observed in the muscle, gills and liver. Overall results suggested that long-term H₂O₂ exposure induced oxidative stress, ER stress and apoptosis in the majority of tested tissues of common carp. The Nrf2, IRE1, PERK and MAPK pathways played important roles in H₂O₂-induced toxicity in fish. These data enriched the toxicity mechanism of H₂O₂ in fish, which might contribute to the risk assessment of H₂O₂ in aquatic environment.

过氧化氢（H ₂ O ₂）在天然水中似乎无处不在。较高的H ₂ O ₂含量可引起水生动物生理应激，免疫抑制甚至死亡，但对H ₂ O ₂毒性的生理和分子机制尚未深入研究。因此，本研究的目的是通过评估对鲤鱼氧化还原状态，细胞凋亡和内质网（ER）胁迫的影响来暴露H ₂ O _2的潜在毒性机制。将鱼置于四种浓度的H ₂ O _2中（0、0.25、0.5和1 mM），持续14天。然后收集血液，肝脏，肌肉，g，肠，心脏，肾脏和脾等组织，以测量生化参数和基因表达。结果表明，H ₂ O ₂暴露抑制了血清，肝脏，肌肉和肠道中的大多数抗氧化参数，但提高了g中的T-SOD，CAT和T-AOC水平。在所有测试的组织中，H ₂ O ₂暴露可显着促进MDA含量。与氧化应激相关的基因，包括nrf2，gstα，sod，cat和/或gpx1H ₂ O ₂暴露后，肝脏，g，肌肉，肠和/或肾脏中的蛋白被上调，而心脏中的蛋白被下调。此外，除了肠道和脾脏外，所有组织中的H ₂ O ₂暴露均抑制了ho-1 mRNA的水平。暴露14天后，H ₂ O ₂诱导内质网应激，并启动IRE1和PERK途径，从而激活下游基因，包括chop，grp78和/或xbp1s，以调节肝脏，腮，肌肉和/或心脏中的UPR。同时，H ₂ O ₂暴露激活了MAPK途径来调节线粒体相关基因，包括bcl-2，bax和cytc进一步触发cas-8，cas-9和cas-3，并加速肝，腮，肌肉和心脏的凋亡。重要的是，在不同的组织中，与氧化应激，内质网应激和凋亡相关的基因表现出不同的影响，并且在肌肉，腮和肝脏中观察到更显着的影响。总体结果表明，长期暴露于H ₂ O _2会在大多数被检鲤组织中引起氧化应激，ER应激和细胞凋亡。Nrf2，IRE1，PERK和MAPK途径在H ₂ O _2中起重要作用在鱼中引起的毒性。这些数据丰富了鱼类中H ₂ O ₂的毒性机制，这可能有助于水生环境中H ₂ O ₂的风险评估。